Azilsartan medoxomil

Identification

Name

Azilsartan medoxomil

Accession Number

DB08822 (DB05358)

Type

Small Molecule

Groups

Approved, Investigational

Description

Azilsartan medoxomil is an angiotensin II receptor antagonist indicated for the treatment of mild to moderate essential hypertension. Azilsartan medoxomil is a prodrug of Azilsartan marketed as "Edarbi" by Takeda. Azilsartan medoxomil has so far been shown to be superior to olmesartan and valsartan in lowering blood pressure.

Pharmacology

Azilsartan medoxomil decreases the pressor effect of angiotensin II. In response, angiotensin I, angiotensin II, and renin are increased while aldosterone is decreased.

Mechanism of action

Azilsartan medoxomil blocks the angiotensin II type 1 receptor preventing angiotensin II from binding and causing vasoconstriction. Azilsartan's ability to remain tightly bound to AT1 receptors for very long periods after drug washout is among its most unusual features.

Azilsartan medoxomil is hydrolyzed to the active metabolite azilsartan in the GI tract. The presence of food does not affect oral absorption of azilsartan medoxomil, and the bioavailability is 60% for azilsartan. Maximum plasma concentrations are reached in 1.5 to 3 hours.

Volume of distribution

Azilsartan medoxomil has a Vd of 16L.

Protein binding

Azilsartan medoxomil is 99% plasma protein bound.

Metabolism

Azilsartan is metabolized by CYP2C9. CYP2C9 carries out decarboxylation of azilsartan to M-I, and O-dealkylation of azilsartan to M-II. Both M-I and M-II have no pharmacologic activity.

Route of elimination

Renal clearance is 2.3 L/minute.

Half life

The half-life is 11 hours, and it takes about 5 days to reach steady state concentrations.